EP1500393A1 - Injectable composition containing taxol - Google Patents

Injectable composition containing taxol Download PDF

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Publication number
EP1500393A1
EP1500393A1 EP04020044A EP04020044A EP1500393A1 EP 1500393 A1 EP1500393 A1 EP 1500393A1 EP 04020044 A EP04020044 A EP 04020044A EP 04020044 A EP04020044 A EP 04020044A EP 1500393 A1 EP1500393 A1 EP 1500393A1
Authority
EP
European Patent Office
Prior art keywords
acid
paclitaxel
acidifying agent
taxol
castor oil
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04020044A
Other languages
German (de)
French (fr)
Inventor
Timothy R. Prout
Hernita Ewald
Paul Handreck
Robyn Elliott
David R. Carver
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mayne Pharma USA Inc
Original Assignee
Mayne Pharma USA Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Application filed by Mayne Pharma USA Inc filed Critical Mayne Pharma USA Inc
Publication of EP1500393A1 publication Critical patent/EP1500393A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • This invention relates to a solution of taxol (paclitaxel) having improved stability.
  • Taxol is a compound extracted from the bark of a western yew, Taxus brevifolia and known for its antineoplastic activity. It is described for example in The Merck Index, Eleventh Edition 1989, monograph 9049.
  • taxol was chosen for development as an antineoplastic agent because of its unique mechanism of action and good cytotoxic activity against IP implanted D16 melanoma and the human X-1 mammary tumor xenograft.
  • Taxol is believed to function as a mitotic spindle poison and as a potent inhibitor of cell replication in vitro. Other mitotic spindle points (colchicine and podophyllotoxin) inhibit microtubule assembly. Taxol employs a different mechanism of action since it appears to shift the equilibrium of polymerimization/depolymerization toward polymer assembly and to stabilize microtubules against depolymerization under conditions which would cause rapid disaggregation of microtubules. The interference with the polymerization/depolymerization cycle in cells appears to interfere with both the replication and migration of cells.
  • taxol After extensive preclinical screening in mouse tumour models, taxol entered clinical trials in 1983. Over the past few years, taxol has demonstrated good response rates in treating both ovarian and breast cancer patients who were not benefiting from vinca alkaloid or cisplatin therapy. It has also shown encouraging results in patients with other types of cancer including lung, melanoma, lymphoma, head and neck.
  • the invention provides a solution containing taxol, cremophor ELTM and ethanol, characterized in that the pH of the solution has been adjusted into the range 1 to 8 by addition of an acid.
  • Acids in the form of powders for example citric acid, are preferred over those which contain water, for example sulfuric acid.
  • the most preferred acid for use in accordance with the present invention is citric acid but a wide range of acids may be used including the following:
  • Taxol Due to its limited solubility in water, Taxol is usually prepared and administered in a vehicle containing cremophor ELTM (a polyethoxylated castor oil which acts as a solubilizer) and ethanol.
  • cremophor ELTM a polyethoxylated castor oil which acts as a solubilizer
  • ethanol a commercially available solution supplied by Bristol-Myers Squibb (BMS) is formulated with these components and has a pH of 9.1.
  • the invention essentially teaches addition of an acid to a taxol formulation to adjust its pH into the range 1 to 8, preferable 5 to 7.
  • Citric acid was dissolved in absolute alcohol, using a ratio of 8mls of absolute alcohol to 1 gram of citric acid, and the solution was stirred for fifteen (15) minutes.
  • Cremophor EL was weighed out into the main mixing vessel.
  • Solution 1 was added to solution 2, and the container used for solution 2 was washed with a minimum quantity of absolute alcohol to ensure complete transfer of the citric acid.
  • Solution 3 was mixed and bubbled with nitrogen for at least 15 minutes.
  • the taxol was weighed out and slurried using absolute alcohol, using a ratio of 8ml of absolute alcohol to 1 gm of taxol.
  • the slurried taxol was added to solution 3 and the slurrying vessel was washed with a minimum quantity of absolute alcohol.
  • Solution 3 was adjusted to 75% of required volume using absolute alcohol, and thoroughly stirred for at least 45 minutes until completely dissolved. Once completely dissolved, the volume, was checked and made up as necessary with absolute alcohol and the final solution stirred for 5 minutes.
  • a solution was prepared with the following formulation: Formulation: (Sample 1) Cremophor EL 0.5mL Citric Acid (Anhydrous) 2.0mg Taxol 6.0mg Absolute Alcohol to 1.0mL The pH of this solution was determined as 6.1.
  • Example 2 Sample 2 per mL Taxol 6.0mg Cremophor EI 0.5mL Absolute Alcohol to 1 mL The solutions were filled into clear type 1 glass 5mL vials and sealed with rubber bungs. The solutions were stored at 40°C for 7 (seven) days and the stability results are shown in Table 1. Sample 1 Sample 2 pH 6.2 9.0 Potency 96.6 86.7 Major individual 0.3% 5.1% impurity Total impurities 2.0% 12.2%
  • the solution was filled into clear type I glass 5mL vials and sealed with rubber bungs.
  • the solution was stored at 40°C for 7 days.

Abstract

A composition of taxol and polyethoxylated castor oil is pH balanced to have a pH less than 8.1 to improve stability. This composition can include an acid, preferably citric acid, to adjust the pH value. The invention includes a method of formulating a taxol solution for injection by mixing an acid with a carrier material, such as castor oil, to form a carrier solution after which taxol is mixed with the carrier solution to form the taxol solution at a pH of less than 8.1. The method may include the step of slurrying the taxol in alcohol before mixing with the carrier solution.

Description

    INJECTABLE COMPOSITION
  • This invention relates to a solution of taxol (paclitaxel) having improved stability.
    • BACKGROUND OF THE INVENTION
  • Taxol is a compound extracted from the bark of a western yew, Taxus brevifolia and known for its antineoplastic activity. It is described for example in The Merck Index, Eleventh Edition 1989, monograph 9049.
  • In 1977, taxol was chosen for development as an antineoplastic agent because of its unique mechanism of action and good cytotoxic activity against IP implanted D16 melanoma and the human X-1 mammary tumor xenograft.
  • Taxol is believed to function as a mitotic spindle poison and as a potent inhibitor of cell replication in vitro. Other mitotic spindle points (colchicine and podophyllotoxin) inhibit microtubule assembly. Taxol employs a different mechanism of action since it appears to shift the equilibrium of polymerimization/depolymerization toward polymer assembly and to stabilize microtubules against depolymerization under conditions which would cause rapid disaggregation of microtubules. The interference with the polymerization/depolymerization cycle in cells appears to interfere with both the replication and migration of cells.
  • After extensive preclinical screening in mouse tumour models, taxol entered clinical trials in 1983. Over the past few years, taxol has demonstrated good response rates in treating both ovarian and breast cancer patients who were not benefiting from vinca alkaloid or cisplatin therapy. It has also shown encouraging results in patients with other types of cancer including lung, melanoma, lymphoma, head and neck.
  • For further information, reference may be made to the US National Cancer Institute's Clinical Brochure for Taxol, revised July 1991, and papers presented at the Second National Cancer Institute Workshop on Taxol and Taxus held in Alexandria, Virginia USA on September 23-24, 1992.
    • BRIEF DESCRIPTION OF THE INVENTION
  • It is a disadvantage of the known formulation that the taxol therein degrades, with the result that the shelf life of the formulation is unsatisfactory, and there is therefore a need for a taxol solution of improved stability.
  • Accordingly, in a general aspect the invention provides a solution containing taxol, cremophor EL™ and ethanol, characterized in that the pH of the solution has been adjusted into the range 1 to 8 by addition of an acid. Acids in the form of powders, for example citric acid, are preferred over those which contain water, for example sulfuric acid. The most preferred acid for use in accordance with the present invention is citric acid but a wide range of acids may be used including the following:
  • Citric acid - monohydrous
  • Citric acid - anhydrous
  • Citric acid - hydrous
  • Acetic acid
  • Formic acid
  • Ascorbic acid
  • Aspartic acid
  • Benzene sulphonic acid
  • Benzoic acid
  • Hydrochloric acid
  • Sulphuric acid
  • Phosphoric acid
  • Nitric acid
  • Tartaric acid
  • Diatrizoic acid
  • Glutamic acid
  • Lactic acid
  • Maleic acid
  • Succinic acid
    • DETAILED DESCRIPTION OF THE INVENTION
  • Due to its limited solubility in water, Taxol is usually prepared and administered in a vehicle containing cremophor EL™ (a polyethoxylated castor oil which acts as a solubilizer) and ethanol. A commercially available solution supplied by Bristol-Myers Squibb (BMS) is formulated with these components and has a pH of 9.1.
  • As indicated above, the invention essentially teaches addition of an acid to a taxol formulation to adjust its pH into the range 1 to 8, preferable 5 to 7.
  • In a preferred procedure adopted by the applicant, which it will be clearly understood is non-limiting, the following steps were carried out:
    • Mixing Instructions SOLUTION 1
  • Citric acid was dissolved in absolute alcohol, using a ratio of 8mls of absolute alcohol to 1 gram of citric acid, and the solution was stirred for fifteen (15) minutes.
    • SOLUTION 2
  • Cremophor EL was weighed out into the main mixing vessel.
    • SOLUTION 3
  • Solution 1 was added to solution 2, and the container used for solution 2 was washed with a minimum quantity of absolute alcohol to ensure complete transfer of the citric acid. Solution 3 was mixed and bubbled with nitrogen for at least 15 minutes. The taxol was weighed out and slurried using absolute alcohol, using a ratio of 8ml of absolute alcohol to 1 gm of taxol. The slurried taxol was added to solution 3 and the slurrying vessel was washed with a minimum quantity of absolute alcohol. Solution 3 was adjusted to 75% of required volume using absolute alcohol, and thoroughly stirred for at least 45 minutes until completely dissolved. Once completely dissolved, the volume, was checked and made up as necessary with absolute alcohol and the final solution stirred for 5 minutes.
    • Example 1
  • A solution was prepared with the following formulation:
    Formulation: (Sample 1)
    Cremophor EL 0.5mL
    Citric Acid (Anhydrous) 2.0mg
    Taxol 6.0mg
    Absolute Alcohol to 1.0mL
    The pH of this solution was determined as 6.1.
  • The stability of this sample was compared with a sample prepared by the formulation stated in the NCl Taxol Clinical brochure (as follows) which had a pH of 9.1. (Sample 2)
    Sample 2 per mL
    Taxol 6.0mg
    Cremophor EI 0.5mL
    Absolute Alcohol to 1 mL
    The solutions were filled into clear type 1 glass 5mL vials and sealed with rubber bungs.
    The solutions were stored at 40°C for 7 (seven) days and the stability results are shown in Table 1.
    Sample 1 Sample 2
    pH 6.2 9.0
    Potency 96.6 86.7
    Major individual 0.3% 5.1% impurity
    Total impurities 2.0% 12.2%
  • Clearly Sample 1 showed significantly increased stability over Sample 2.
    • Example 2
  • A solution was prepared with the following formulation:
    Formulation: (Sample 3)
    Cremophor EL 0.5mL
    Taxol 6.0mg
    Absolute Ethanol to 1mL
  • pH adjusted to 6.6 with 1.0M Acetic Acid.
  • The solution was filled into clear type I glass 5mL vials and sealed with rubber bungs.
  • The solution was stored at 40°C for 7 days.
  • The stability results obtained are compared to those seen with Sample 2.
    Sample 3 Sample 2
    pH 6.7 9.0
    Potency 97.5 86.7
    Major individual 0.3% 5.1% impurity
    Total impurities 2.3% 12.2%
  • Again the significantly superior stability of the formulation according to the invention (Sample 3) is evident.
  • It will be clearly understood that the invention in its general aspects is not limited to the specific details referred to hereinabove.

Claims (33)

  1. A stabiliser formulation for use in combination with, and as a vehicle for, paclitaxel to form a pharmaceutical for use in treating cancer said formulation comprising polyethoxylated castor oil and an acidifying agent.
  2. A formulation as claimed in claim 1 wherein the acidifying agent is formic acid, ascorbic acid, aspartic acid, benzene sulphonic acid, benzoic acid, hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, tartaric acid, diatrizoic acid, glutamic acid, lactic acid, maleic acid, succinic acid, acetic acid, citric acid or anhydrous citric acid, including such agents in particulate solid form.
  3. A formulation as claimed in claim 1 or claim 2 and including ethanol as a constituent thereof.
  4. A formulation as claimed in claim 1 and comprising:-
    (i) polyethoxylated castor oil as a solubilizer for paclitaxel,
    (ii) citric acid as an acidifying agent, and
    (iii) optionally ethanol
  5. A composition comprising:-
    paclitaxel;
    castor oil; and
    anhydrous citric acid in sufficient amounts to adjust the pH of the composition to less than 8.1.
  6. A pharmaceutical composition suitable for use in treating cancer and comprising paclitaxel, polyethoxylated castor oil and an acidifying agent, the components of the composition being mixed in such proportion that said composition has a resulting pH less than 8.1.
  7. A pharmaceutical composition as claimed in claim 6 wherein the proportion of the acidifying agent is such that the pH of the composition is from 5 to 7.
  8. A pharmaceutical composition as claimed in claim 6 or claim 7 and including ethanol or other alcohol as a constituent thereof.
  9. A pharmaceutical composition as claimed in any one of claims 6 to 8 wherein the acidifying agent is formic acid, ascorbic acid, aspartic acid, benzene sulphonic acid, benzoic acid, hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, tartaric acid, diatrizoic acid, glutamic acid, lactic acid, maleic acid or succinic acid.
  10. A pharmaceutical composition as claimed in any one of claims 6 to 8 wherein the acidifying agent is acetic acid or citric acid.
  11. A pharmaceutical composition as claimed in claim 10 wherein the acidifying agent is anhydrous citric acid.
  12. A pharmaceutical composition as claimed in any of claims 6 to 11 wherein the acidifying agent is an acid in particulate solid form.
  13. A pharmaceutical composition as claimed in claim 6 and comprising:-
    (i) paclitaxel;
    (ii) polyethoxylated castor oil as a solubilizer for the paclitaxel;
    (iii) citric acid as an acidifying agent present in such an amount that the composition as a whole has a pH of from 1 to 8, and
    (iv) optionally ethanol.
  14. Use of an acidifying agent as a stabilizer for paclitaxel in a pharmaceutical composition in which said paclitaxel is carried by polyethoxylated castor oil, said acidifying agent being employed in such use in such proportion that said composition has a resulting pH less than 8.1.
  15. Use as claimed in claim 13 wherein the acidifying agent is as defined in any one of claims 9 to 12.
  16. Use as claimed in claim 14 or claim 15 and including ethanol as a constituent of the pharmaceutical composition.
  17. Use as claimed in any one of claims 14 to 16 wherein the proportion of the acidifying agent is such that the pH of the acidified stabilized pharmaceutical composition is from 5 to 7.
  18. Use as claimed in claim 14 wherein the acidified stabilized pharmaceutical composition comprises:-
    (i) paclitaxel;
    (ii) polyethoxylated castor oil as a solubilizer for paclitaxel;
    (iii) citric acid as the acidifying agent, said acidifying agent being present in such an amount that the acidified stabilized pharmaceutical composition as a whole has a pH of from 1 to 8, and
    (iv) optionally ethanol.
  19. Use of an acidifying agent for the manufacture of a medicament which comprises paclitaxel and polyethoxylated castor oil as well as said acidifying agent, which medicament has a pH less than 8.1 and which is for the treatment of cancer.
  20. Use of castor oil for the manufacture of a medicament for use in the treatment of cancer, said medicament being in the form of a composition comprising citric acid, paclitaxel and polyethoxylated castor oil and having a pH of less than 8.1.
  21. A method of formulating a taxol solution for injection, the method comprising:-
    (i) mixing an acid material with a carrier material to form a carrier solution; and
    (ii) mixing paclitaxel with the carrier solution to form a paclitaxel solution having a pH of less than 8.1 whereby the paclitaxel in the paclitaxel solution does not readily degrade.
  22. A method as claimed in claim 21 wherein said paclitaxel solution has a pH of from 5 to 7.
  23. A method as claimed in claim 21 or claim 22 wherein said acid material is an acidifying agent as defined in any one of claims 9 to 12.
  24. A method as claimed in any one of claims 21 to 23 wherein said carrier material comprises polyethoxylated castor oil.
  25. A method as claimed in claim 24 wherein said carrier material includes ethanol as a constituent thereof.
  26. A method as claimed in any one of claims 21 to 25 and including the step of slurrying said paclitaxel in ethanol before mixing said paclitaxel with the carrier solution.
  27. A composition comprising taxol in a polyethoxylated castor oil wherein said composition has a pH less than 8.1.
  28. A method of formulating a taxol solution for injection in which the taxol does not readily degrade, comprising the following steps:
    mixing acid with a carrier material to form a first carrier solution; and
    mixing taxol with the first carrier solution to form a taxol solution having a pH of less than 8.1 whereby the taxol in the taxol solution does not readily degrade.
  29. A method according to claim 28 wherein said acid is acetic acid.
  30. A method according to claim 28 wherein said acid is a citric acid.
  31. A method according to claim 28 wherein said carrier material is polyethoxylated castor oil.
  32. A method according to claim 28 including the step of slurrying said taxol in alcohol before mixing said taxol with the first carrier solution.
  33. A composite comprising:
    taxol;
    castor oil; and
    anhydrous citric acid in sufficient amounts to adjust the pH of the composition to less than 8.1.
EP04020044A 1992-11-27 1993-11-18 Injectable composition containing taxol Withdrawn EP1500393A1 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
AUPL607492 1992-11-27
AUPL607492 1992-11-27
US99550192A 1992-12-22 1992-12-22
US995501 1992-12-22
EP94901593A EP0674510B1 (en) 1992-11-27 1993-11-18 Injectable composition comprising paclitaxel
EP97121710A EP0835657B1 (en) 1992-11-27 1993-11-18 Stable injectable paclitaxel composition

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP97121710A Division EP0835657B1 (en) 1992-11-27 1993-11-18 Stable injectable paclitaxel composition

Publications (1)

Publication Number Publication Date
EP1500393A1 true EP1500393A1 (en) 2005-01-26

Family

ID=25644377

Family Applications (4)

Application Number Title Priority Date Filing Date
EP94901593A Revoked EP0674510B1 (en) 1992-11-27 1993-11-18 Injectable composition comprising paclitaxel
EP03025151A Pending EP1384474A1 (en) 1992-11-27 1993-11-18 Injectable composition containing taxol
EP04020044A Withdrawn EP1500393A1 (en) 1992-11-27 1993-11-18 Injectable composition containing taxol
EP97121710A Revoked EP0835657B1 (en) 1992-11-27 1993-11-18 Stable injectable paclitaxel composition

Family Applications Before (2)

Application Number Title Priority Date Filing Date
EP94901593A Revoked EP0674510B1 (en) 1992-11-27 1993-11-18 Injectable composition comprising paclitaxel
EP03025151A Pending EP1384474A1 (en) 1992-11-27 1993-11-18 Injectable composition containing taxol

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP97121710A Revoked EP0835657B1 (en) 1992-11-27 1993-11-18 Stable injectable paclitaxel composition

Country Status (12)

Country Link
US (7) US5733888A (en)
EP (4) EP0674510B1 (en)
JP (1) JP2880292B2 (en)
AT (2) ATE169216T1 (en)
AU (1) AU5612694A (en)
CA (2) CA2308082A1 (en)
DE (2) DE69320206T2 (en)
DK (2) DK0674510T3 (en)
ES (2) ES2119996T3 (en)
GR (1) GR3027724T3 (en)
PT (1) PT835657E (en)
WO (2) WO1994012031A1 (en)

Families Citing this family (105)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE169216T1 (en) * 1992-11-27 1998-08-15 Napro Biotherapeutics Inc INJECTABLE COMPOSITION CONTAINING PACLITAXEL
TW406020B (en) * 1993-09-29 2000-09-21 Bristol Myers Squibb Co Stabilized pharmaceutical composition and its method for preparation and stabilizing solvent
FR2710534B1 (en) * 1994-09-28 1996-07-05 Bristol Myers Squibb Co Stabilization solvent, pharmaceutical composition containing it, and process for its preparation.
NL9500340A (en) * 1995-02-22 1996-10-01 Yew Tree Pharmaceuticals B V Stabilized paclitaxel solution and pharmaceutical preparation containing said solution
DE19536165A1 (en) * 1995-09-28 1997-04-03 Basf Ag Process for cleaning alkoxylated fats
US6245805B1 (en) 1995-10-26 2001-06-12 Baker Norton Pharmaceuticals, Inc. Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents
US6964946B1 (en) 1995-10-26 2005-11-15 Baker Norton Pharmaceuticals, Inc. Oral pharmaceutical compositions containing taxanes and methods of treatment employing the same
US6395770B1 (en) * 1995-10-26 2002-05-28 Baker Norton Pharmaceuticals, Inc. Method and compositions for administering taxanes orally to human patients
WO1997023208A1 (en) * 1995-12-21 1997-07-03 Genelabs Technologies, Inc. Taxane composition and method
US20030157187A1 (en) * 1996-12-02 2003-08-21 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing inflammatory diseases
US6515016B2 (en) 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
AU741439B2 (en) 1996-12-30 2001-11-29 Battelle Memorial Institute Formulation and method for treating neoplasms by inhalation
US20030087954A1 (en) * 1997-01-07 2003-05-08 Sonus Pharmaceuticals, Inc. Method of treating bladder carcinoma using a Taxane/Tocopherol formulation
US6727280B2 (en) * 1997-01-07 2004-04-27 Sonus Pharmaceuticals, Inc. Method for treating colorectal carcinoma using a taxane/tocopherol formulation
US6458373B1 (en) * 1997-01-07 2002-10-01 Sonus Pharmaceuticals, Inc. Emulsion vehicle for poorly soluble drugs
US20030105156A1 (en) * 1997-01-07 2003-06-05 Nagesh Palepu Method for administration of a taxane/tocopherol formulation to enhance taxane therapeutic utility
BE1011216A3 (en) * 1997-06-13 1999-06-01 Thissen En Abrege L T B Lab Pharmaceutical form for the administration of paclitaxel, method of preparation of a composition paclitaxel ready to employment and use thereof.
IL131217A0 (en) * 1998-03-10 2001-01-28 Napro Biotherapeutics Inc Novel methods and compositions for delivery of taxanes
US5922754A (en) * 1998-10-02 1999-07-13 Abbott Laboratories Pharmaceutical compositions containing paclitaxel
AU1214400A (en) 1998-10-20 2000-05-08 Ben Venue Laboratories, Inc. Process for purification of solvents useful in the preparation of pharmaceuticalcompositions
US6071952A (en) * 1998-12-02 2000-06-06 Mylan Pharmaceuticals, Inc. Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
US6040330A (en) * 1999-01-08 2000-03-21 Bionumerik Pharmaceuticals, Inc. Pharmaceutical formulations of taxanes
US6410255B1 (en) * 1999-05-05 2002-06-25 Aurora Biosciences Corporation Optical probes and assays
EP1591437B1 (en) 1999-05-14 2009-11-25 Nereus Pharmaceuticals, Inc. Interleukin-1 and tumor necrosis factor-alpha modulators, syntheses of said modulators and methods of using said modulators
DE19925211B4 (en) * 1999-06-01 2006-01-12 PBS Pharmaceutical Bulk Substances SA Kit for the preparation of a formulation of paclitaxel
AR027519A1 (en) * 2000-01-20 2003-04-02 Baker Norton Pharma PURIFICATION OF POLYOXYETHYLED CASTOR OILS WITH ACTIVATED CARBON
US6638973B2 (en) * 2000-02-02 2003-10-28 Fsu Research Foundation, Inc. Taxane formulations
US20040171107A1 (en) * 2000-02-23 2004-09-02 David Nelson Modified flourescent proteins
JP4922507B2 (en) * 2000-08-10 2012-04-25 武田薬品工業株式会社 Pharmaceutical composition
AU2001278705A1 (en) 2000-08-10 2002-02-25 Takeda Chemical Industries Ltd. Pharmaceutical composition
JP4395549B2 (en) * 2000-11-16 2010-01-13 ザ レジェンツ オブ ザ ユニヴァースティ オブ カリフォルニア Marine actinomycete taxa for the discovery of drugs and fermentation products
AU2002239282A1 (en) * 2000-11-28 2002-06-11 Transform Pharmaceuticals, Inc. Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof
WO2002080940A2 (en) 2001-04-06 2002-10-17 Cytorex Biosciences, Inc. Pharmacologically active strong acid solutions
KR100774366B1 (en) * 2001-09-10 2007-11-08 주식회사 중외제약 Injectable composition of paclitaxel
EP1461056A4 (en) * 2001-11-26 2006-01-25 Supergen Inc Method for preparing and using polyoxyethylated castor oil in pharmaceutical compositions
US20040092428A1 (en) * 2001-11-27 2004-05-13 Hongming Chen Oral pharmaceuticals formulation comprising paclitaxel, derivatives and methods of administration thereof
US6476068B1 (en) * 2001-12-06 2002-11-05 Pharmacia Italia, S.P.A. Platinum derivative pharmaceutical formulations
RS52904A (en) * 2001-12-20 2006-12-15 Bristol-Myers Squib Company Pharmaceutical compositions of orally active taxane derivatives having enhanced bioavailability
CZ294371B6 (en) * 2002-06-10 2004-12-15 Pliva - Lachema, A. S. Stabilized pharmaceutical composition based on polyoxyethylated castor oil and process for preparing thereof
US7176232B2 (en) 2002-06-24 2007-02-13 The Regents Of The University Of California Salinosporamides and methods for use thereof
DK1530465T4 (en) * 2002-06-26 2016-03-21 Medigene Ag A method of producing a cationic liposomal preparation comprising a lipophilic compound.
NZ538433A (en) * 2002-08-02 2008-02-29 Nereus Pharmaceuticals Inc Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
US7935704B2 (en) * 2003-08-01 2011-05-03 Nereus Pharmaceuticals, Inc. Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
US7919497B2 (en) 2002-08-02 2011-04-05 Nereus Pharmaceuticals, Inc. Analogs of dehydrophenylahistins and their therapeutic use
WO2004034970A2 (en) * 2002-09-27 2004-04-29 Nereus Pharmaceuticals, Inc. Macrocyclic lactams
AU2003291458A1 (en) * 2002-11-08 2004-06-03 Bristol-Myers Squibb Company Pharmaceutical compositions and methods of using taxane derivatives
WO2004072104A2 (en) * 2003-02-11 2004-08-26 Northwestern University Methods and materials for nanocrystalline surface coatings and attachment of peptide amphiphile nanofibers thereon
MXPA05013982A (en) * 2003-06-20 2006-05-25 Nereus Pharmaceuticals Inc Use of [3.2.0] heterocyclic compounds and analogs thereof for the treatment of cancer, inflammation and infectious diseases.
NZ544858A (en) * 2003-06-20 2009-07-31 Univ California Salinosporamides and methods for use thereof
US20050016926A1 (en) * 2003-07-24 2005-01-27 Dabur Research Foundation Stabilized formulation
US7619059B2 (en) * 2003-07-29 2009-11-17 Life Technologies Corporation Bimolecular optical probes
US7727752B2 (en) * 2003-07-29 2010-06-01 Life Technologies Corporation Kinase and phosphatase assays
CA2445420A1 (en) * 2003-07-29 2005-01-29 Invitrogen Corporation Kinase and phosphatase assays
US20050208095A1 (en) * 2003-11-20 2005-09-22 Angiotech International Ag Polymer compositions and methods for their use
ES2325506T3 (en) * 2003-12-12 2009-09-07 Quiral Quimica Do Brasil PROCEDURE FOR THE PREPARATION OF PHARMACEUTICAL ACTIVE PRINCIPLES (API) ANHYDRATES AND HYDRATES; STABLE PHARMACEUTICAL COMPOSITIONS PREPARED FROM THE SAME AND USES OF SUCH COMPOSITIONS.
ATE509018T1 (en) * 2004-01-23 2011-05-15 Nereus Pharmaceuticals Inc BISINDOLPYRROLES SUITABLE AS ANTIMICROBIAL AGENT
KR20050099311A (en) * 2004-04-09 2005-10-13 에이엔에이치 케어연구소(주) Composition for injection comprising anticancer drug
US7579371B2 (en) 2004-04-30 2009-08-25 Nereus Pharmaceuticals, Inc. Methods of using [3.2.0] heterocyclic compounds and analogs thereof
JP2007535559A (en) 2004-04-30 2007-12-06 ネレアス ファーマシューティカルズ インコーポレイテッド [3.2.0] Heterocyclic compounds and methods of use thereof
US7361683B2 (en) 2004-11-24 2008-04-22 Yung Shin Pharm. Ind., Co., Ltd Paclitaxel aqueous injection solution and methods for preparing the same
AU2005311709B2 (en) 2004-12-03 2011-07-28 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating neoplastic diseases
WO2006126825A1 (en) * 2005-05-23 2006-11-30 Choongwae Pharma Corporation Composition comprising tetrafluorobenzyl derivatives or salts of thereof for injection
KR20080030024A (en) * 2005-06-17 2008-04-03 호스피라 오스트레일리아 피티와이 리미티드 Liquid pharmaceutical formulations of docetaxel
EP2311795A3 (en) 2005-07-21 2011-12-28 Nereus Pharmaceuticals, Inc. Interleukin-1 and tumor necrosis factor-alpha modulators; syntheses of such modulators and methods of using such modulators
TWI429452B (en) 2005-08-31 2014-03-11 Abraxis Bioscience Llc Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents
KR101457834B1 (en) 2005-08-31 2014-11-05 아브락시스 바이오사이언스, 엘엘씨 Compositions and methods for preparation of poorly water soluble drugs with increased stability
BRPI0600194A (en) * 2006-01-30 2007-10-23 Quiral Quimica Do Brasil S A docetaxel-containing pharmaceutical compositions and a degradation inhibitor and process for obtaining same
US8129527B2 (en) * 2006-11-03 2012-03-06 Nereus Pharmacuticals, Inc. Analogs of dehydrophenylahistins and their therapeutic use
US7824698B2 (en) * 2007-02-02 2010-11-02 Nereus Pharmaceuticals, Inc. Lyophilized formulations of Salinosporamide A
FR2912745A1 (en) * 2007-02-19 2008-08-22 Centre Nat Rech Scient NEW INDOLE-DERIVED COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US20090017167A1 (en) * 2007-07-11 2009-01-15 Herbalife International Inc. Mixture and beverage made therefrom for protecting cellular hydration
US8394816B2 (en) * 2007-12-07 2013-03-12 Irene Ghobrial Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia
KR101053780B1 (en) * 2008-02-29 2011-08-02 동아제약주식회사 Single liquid stable pharmaceutical composition containing docetaxel
JP2011519975A (en) * 2008-05-12 2011-07-14 ネレアス ファーマシューティカルズ インコーポレイテッド Salinosporamide derivatives as proteasome inhibitors
ES2344674B1 (en) 2008-08-07 2011-06-29 Gp Pharm, S.A. INJECTABLE PHARMACEUTICAL COMPOSITION OF TAXANOS.
US9198968B2 (en) 2008-09-15 2015-12-01 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8114429B2 (en) 2008-09-15 2012-02-14 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8257722B2 (en) 2008-09-15 2012-09-04 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8128951B2 (en) 2008-09-15 2012-03-06 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
TWI438009B (en) * 2010-02-19 2014-05-21 Teikoku Pharma Usa Inc Taxane pro-emulsion formulations and methods making and using the same
EA027666B1 (en) 2010-05-03 2017-08-31 ТЕИКОКУ ФАРМА ЮСЭй, ИНК. Non-aqueous taxane pro-emulsion formulations and methods of making and using the same
KR101844623B1 (en) 2011-03-29 2018-04-02 사노피 Otamixaban formulations with improved stability
EP2731938A4 (en) * 2011-07-11 2014-12-24 Biolyse Pharma Corp Novel anti-cancer isocarbostyril alkaloid conjugates
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
JO3685B1 (en) 2012-10-01 2020-08-27 Teikoku Pharma Usa Inc Non-aqueous taxane nanodispersion formulations and methods of using the same
EP2777691A1 (en) 2013-03-14 2014-09-17 Pharmachemie B.V. Taxoid - Purification of Liquid Excipients
AU2014239516B2 (en) * 2013-03-15 2019-01-24 Epizyme, Inc. Injectable formulations for treating cancer
US10525171B2 (en) 2014-01-24 2020-01-07 The Spectranetics Corporation Coatings for medical devices
WO2016036674A1 (en) 2014-09-02 2016-03-10 Bhupinder Singh Deuterated or a non-deuterated molecule and pharmaceutical formulations
WO2016044649A1 (en) * 2014-09-17 2016-03-24 Epizyme, Inc. Injectable formulations for treating cancer
US10751317B2 (en) 2014-10-08 2020-08-25 Pacific Northwest Research Institute Methods and compositions for increasing the potency of antifungal agents
KR102623404B1 (en) 2015-03-06 2024-01-11 비욘드스프링 파마수티컬스, 인코포레이티드. How to Treat Brain Tumors
WO2016144635A1 (en) 2015-03-06 2016-09-15 Beyondspring Pharmaceuticals, Inc. Method of treating cancer associated with a ras mutation
AU2016291708B2 (en) 2015-07-13 2020-12-24 Beyondspring Pharmaceuticals, Inc Plinabulin compositions
US10561766B2 (en) 2015-09-15 2020-02-18 W. L. Gore & Associates, Inc. Drug composition and coating
IL260933B2 (en) 2016-02-08 2023-04-01 Beyondspring Pharmaceuticals Inc Plinabulin compositions
EP3463337A4 (en) 2016-06-06 2020-02-12 Beyondspring Pharmaceuticals, Inc. Composition and method for reducing neutropenia
US11633393B2 (en) 2017-01-06 2023-04-25 Beyondspring Pharmaceuticals, Inc. Tubulin binding compounds and therapeutic use thereof
WO2018144764A1 (en) 2017-02-01 2018-08-09 Beyondspring Pharmaceuticals, Inc. Method of reducing neutropenia
US10226423B1 (en) * 2017-12-20 2019-03-12 RxOMEG Therapeutics LLC Colchicine drug-to-drug interactions
CN112135614A (en) 2018-01-24 2020-12-25 大连万春布林医药有限公司 Compositions and methods for reducing thrombocytopenia by administering plinabulin
EP3773612A4 (en) 2018-03-28 2022-01-12 Herbalife International of America, Inc. Acetylation of polysaccharides
SG11202100854TA (en) * 2018-10-16 2021-05-28 US Nano Food & Drug INC Intratumor injection formulation
AU2021257738A1 (en) 2020-04-13 2022-05-19 US Nano Food & Drug INC Basic chemotherapeutic intratumour injection formulation

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0253738A1 (en) * 1986-07-17 1988-01-20 Rhone-Poulenc Sante Taxol derivatives, their preparation and pharmaceutical compositions containing them
US4960790A (en) * 1989-03-09 1990-10-02 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
EP0522936A1 (en) * 1991-07-08 1993-01-13 Aventis Pharma S.A. Taxane derivatives containing compositions
WO1994012198A1 (en) * 1992-11-27 1994-06-09 F.H. Faulding & Co. Limited Injectable taxol composition
WO1994012030A1 (en) * 1992-11-27 1994-06-09 Napro Biotherapeutics, Inc. Injectable composition

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS552421B2 (en) * 1971-08-06 1980-01-19
US4942184A (en) * 1988-03-07 1990-07-17 The United States Of America As Represented By The Department Of Health And Human Services Water soluble, antineoplastic derivatives of taxol
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
US5136060A (en) * 1989-11-14 1992-08-04 Florida State University Method for preparation of taxol using an oxazinone
CA2051660C (en) * 1990-02-15 2001-04-17 Jed C. Seybold Method of frying oil treatment using an alumina and amorphous silica composition
TW223634B (en) * 1991-03-18 1994-05-11 Kingston David G I
US5254580A (en) * 1993-01-19 1993-10-19 Bristol-Myers Squibb Company 7,8-cyclopropataxanes
US5281727A (en) * 1992-11-27 1994-01-25 Napro Biotherapeutics, Inc. Method of using ion exchange media to increase taxane yields
TW406020B (en) * 1993-09-29 2000-09-21 Bristol Myers Squibb Co Stabilized pharmaceutical composition and its method for preparation and stabilizing solvent
US5733388A (en) 1994-08-11 1998-03-31 Daido Tokiushuko Kabushiki Kaisha Steel composition for bearings and method of producing the same

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0253738A1 (en) * 1986-07-17 1988-01-20 Rhone-Poulenc Sante Taxol derivatives, their preparation and pharmaceutical compositions containing them
US4960790A (en) * 1989-03-09 1990-10-02 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
EP0522936A1 (en) * 1991-07-08 1993-01-13 Aventis Pharma S.A. Taxane derivatives containing compositions
EP0522937A1 (en) * 1991-07-08 1993-01-13 Aventis Pharma S.A. Taxane derivatives containing compositions
WO1994012198A1 (en) * 1992-11-27 1994-06-09 F.H. Faulding & Co. Limited Injectable taxol composition
WO1994012030A1 (en) * 1992-11-27 1994-06-09 Napro Biotherapeutics, Inc. Injectable composition

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TARR, BRYAN D. ET AL: "A new parenteral vehicle for the administration of some poorly water soluble anti-cancer drugs", XP002301609, retrieved from STN Database accession no. 106:182581 *
E.K.ROWINSKY ET AL.: "TAXOL: A NOVEL INVESTIGATIONAL ANTIMICROTUBULE AGENT", JOURNAL OF THE NATIONAL CANCER INSTITUTE, vol. 82, no. 15, 1 August 1990 (1990-08-01), pages 1247 - 1259, XP002054343 *
JOURNAL OF PARENTERAL SCIENCE AND TECHNOLOGY , 41(1), 31-3 CODEN: JPATDS; ISSN: 0279-7976, 1987 *

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